The proposed research will be a continuation of work in progress evaluating the role of the phagocytic system in host defense against serious microbial disease. Functional studies will include evaluation of the metabolic response of phagocytizing granulocytes and monocytes. The chemiluminescence assay will be a primary tool for studying the metabolic response of phagocytic cells. Investigation of the source of chemiluminescence continues to increase evidence that this response of phagocytic cells is closely associated with microbicidal activity within phagocytic vacuoles. Molecular probes such as ionophore, singlet oxygen scavengers, and membrane stimulators will be used to help identify intraleukocyte molecular events which are involved in bacterial and fungal killing. The other functional parameters of phagocytic cells which will be stuided include adherence, phagocytosis and chemotaxis. There will be simultaneous evaluation of these several functions on blood samples from patients with a variety of disorders. Dysfunction will be correlated with clinical manifestations of disease. Patient groups that will be evaluated include newborn infants, patients with chronic granulomatous disease, hyperimmunoglobulin E syndrome, chronic renal dialysis and patients with unexplained susceptibility to infection. Our ultimate goal is to improve the condition of patients with defective phagocytic cell function by finding practical means of restoring function to normal.